title: Identification of potential target genes of butyrate in dimethylhydrazine-induced colorectal cancer in mice.
abstract: The mechanism by which butyrate prevents colorectal cancer (CRC) is unclear. The objective of this study was to identify potential target genes of butyrate in 1,2-dimethylhydrazine (DMH)-induced CRC in mice. Nontumor colorectal tissues of mice from DMH + butyrate, DMH, and control groups were hybridized on Agilent Mouse Whole Genome 44K Oligo Microarrays. Selected genes were validated by qRT-PCR. Data was further analyzed by KEGG, gene ontology (GO), and pathway studio software. The tumor incidence in the DMH + butyrate and DMH groups was 30% and 90%, respectively (P < 0.05). There were 355 genes downregulated due to DMH treatment while upregulated by butyrate, and 475 genes upregulated by DMH while downregulated by butyrate. The results revealed that most of the tumor-related signaling pathways (e.g., MAPK pathway, Wnt pathway, insulin pathway, and VEGF pathway) were downregulated by butyrate. The GO terms related to cell differentiation, cell cycle, cell proliferation, cell death, cell adhesion, and cell migration were significantly affected. The chemopreventive effects of butyrate were confirmed in the DMH-induced CRC mice model. And mechanisms encompassing multiple pathways and GO terms are involved in the regulation of gene expression.
authors.affiliation: a Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine , Shanghai Jiao-Tong University , Shanghai , China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Chen
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Lin
authors.forename: Ji-Lin
authors.initials: JL
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Kong
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.forename: Jing-Yuan
authors.initials: JY
authors.lastname: Fang
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D051379:Mice; D008813:Mice, Inbred ICR; D046228:Microarray Analysis; D015398:Signal Transduction / Q000235:genetics
chemical_list: D002087:Butyrates; D019813:1,2-Dimethylhydrazine